Regularization and Kernelization of the Maximin Correlation Approach

Robust classification becomes challenging when each class consists of multiple subclasses. Examples include multi-font optical character recognition and automated protein function prediction. In correlation-based nearest-neighbor classification, the maximin correlation approach (MCA) provides the worst-case optimal solution by minimizing the maximum misclassification risk through an iterative procedure. Despite the optimality, the original MCA has drawbacks that have limited its wide applicability in practice. That is, the MCA tends to be sensitive to outliers, cannot effectively handle nonlinearities in datasets, and suffers from having high computational complexity. To address these limitations, we propose an improved solution, named regularized maximin correlation approach (R-MCA). We first reformulate MCA as a quadratically constrained linear programming (QCLP) problem, incorporate regularization by introducing slack variables in the primal problem of the QCLP, and derive the corresponding Lagrangian dual. The dual formulation enables us to apply the kernel trick to R-MCA so that it can better handle nonlinearities. Our experimental results demonstrate that the regularization and kernelization make the proposed R-MCA more robust and accurate for various classification tasks than the original MCA. Furthermore, when the data size or dimensionality grows, R-MCA runs substantially faster by solving either the primal or dual (whichever has a smaller variable dimension) of the QCLP.Comment: Submitted to IEEE Acces

Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening

This work introduces a number of algebraic topology approaches, such as multicomponent persistent homology, multi-level persistent homology and electrostatic persistence for the representation, characterization, and description of small molecules and biomolecular complexes. Multicomponent persistent homology retains critical chemical and biological information during the topological simplification of biomolecular geometric complexity. Multi-level persistent homology enables a tailored topological description of inter- and/or intra-molecular interactions of interest. Electrostatic persistence incorporates partial charge information into topological invariants. These topological methods are paired with Wasserstein distance to characterize similarities between molecules and are further integrated with a variety of machine learning algorithms, including k-nearest neighbors, ensemble of trees, and deep convolutional neural networks, to manifest their descriptive and predictive powers for chemical and biological problems. Extensive numerical experiments involving more than 4,000 protein-ligand complexes from the PDBBind database and near 100,000 ligands and decoys in the DUD database are performed to test respectively the scoring power and the virtual screening power of the proposed topological approaches. It is demonstrated that the present approaches outperform the modern machine learning based methods in protein-ligand binding affinity predictions and ligand-decoy discrimination

A topological approach for protein classification

Protein function and dynamics are closely related to its sequence and structure. However prediction of protein function and dynamics from its sequence and structure is still a fundamental challenge in molecular biology. Protein classification, which is typically done through measuring the similarity be- tween proteins based on protein sequence or physical information, serves as a crucial step toward the understanding of protein function and dynamics. Persistent homology is a new branch of algebraic topology that has found its success in the topological data analysis in a variety of disciplines, including molecular biology. The present work explores the potential of using persistent homology as an indepen- dent tool for protein classification. To this end, we propose a molecular topological fingerprint based support vector machine (MTF-SVM) classifier. Specifically, we construct machine learning feature vectors solely from protein topological fingerprints, which are topological invariants generated during the filtration process. To validate the present MTF-SVM approach, we consider four types of problems. First, we study protein-drug binding by using the M2 channel protein of influenza A virus. We achieve 96% accuracy in discriminating drug bound and unbound M2 channels. Additionally, we examine the use of MTF-SVM for the classification of hemoglobin molecules in their relaxed and taut forms and obtain about 80% accuracy. The identification of all alpha, all beta, and alpha-beta protein domains is carried out in our next study using 900 proteins. We have found a 85% success in this identifica- tion. Finally, we apply the present technique to 55 classification tasks of protein superfamilies over 1357 samples. An average accuracy of 82% is attained. The present study establishes computational topology as an independent and effective alternative for protein classification

TopologyNet: Topology based deep convolutional neural networks for biomolecular property predictions

Although deep learning approaches have had tremendous success in image, video and audio processing, computer vision, and speech recognition, their applications to three-dimensional (3D) biomolecular structural data sets have been hindered by the entangled geometric complexity and biological complexity. We introduce topology, i.e., element specific persistent homology (ESPH), to untangle geometric complexity and biological complexity. ESPH represents 3D complex geometry by one-dimensional (1D) topological invariants and retains crucial biological information via a multichannel image representation. It is able to reveal hidden structure-function relationships in biomolecules. We further integrate ESPH and convolutional neural networks to construct a multichannel topological neural network (TopologyNet) for the predictions of protein-ligand binding affinities and protein stability changes upon mutation. To overcome the limitations to deep learning arising from small and noisy training sets, we present a multitask topological convolutional neural network (MT-TCNN). We demonstrate that the present TopologyNet architectures outperform other state-of-the-art methods in the predictions of protein-ligand binding affinities, globular protein mutation impacts, and membrane protein mutation impacts.Comment: 20 pages, 8 figures, 5 table

Lung Disease Classification using Dense Alex Net Framework with Contrast Normalisation and Five-Fold Geometric Transformation

lung disease is one of the leading causes of death worldwide. Most cases of lung diseases are found when the disease is in an advanced stage. Therefore, the development of systems and methods that begin to diagnose quickly and prematurely plays a vital role in today's world. Currently, in detecting differences in lung cancer, an accurate diagnosis of cancer types is needed. However, improving the accuracy and reducing training time of the diagnosis remains a challenge. In this study, we have developed an automated classification scheme for lung cancer presented in histopathological images using a dense Alex Net framework. The proposed methodology carries out several phases includes pre-processing, contrast normalization, data augmentation and classification. Initially, the pre-processing step is accompanied to diminish the noisy contents present in the image. Contrast normalization has been explored to maintain the same illumination factor among histopathological lung images next to pre-processing. Afterwards, data augmentation phase has been carried out to enhance the dataset further to avoid over-fitting problems. Finally, the Dense Alex Net is utilized for classification that comprises five convolutional layers, one multi-scale convolution layer, and three fully connected layers. In evaluation experiments, the proposed approach was trained using our original database to provide rich and meaningful features. The accuracy attained by the proposed methodology is93%, which is maximum compared with the existing algorithm